Unique neuronal functions of cathepsin L and cathepsin B in secretory vesicles: biosynthesis of peptides in neurotransmission and neurodegenerative disease

2006 ◽  
Vol 387 (10/11) ◽  
Author(s):  
Vivian Y.H. Hook
Keyword(s):  
Neurodegenerative Disease ◽  
Cathepsin B ◽  
Cathepsin L ◽  
Secretory Vesicles ◽  
Neuronal Functions

The cysteine proteinases of Schistosoma mansoni cercariae

Parasitology ◽  
1997 ◽  
Vol 114 (2) ◽  
pp. 105-112 ◽  
Author(s):  
J. P. DALTON ◽  
K. A. CLOUGH ◽  
M. K. JONES ◽  
P. J. BRINDLEY
Keyword(s):  
Schistosoma Mansoni ◽  
Cathepsin B ◽  
Cathepsin L ◽  
Serine Proteinase ◽  
Skin Penetration ◽  
Scanning Electron Micrographs ◽  
Cysteine Proteinases ◽  
Similar Function ◽  
Substrate Preferences ◽  
Serine Proteinase Activity

Based on substrate preferences, cercariae of Schistosoma mansoni were seen to express both cathepsin L and cathepsin B cysteine proteinases, although the former activity was many -fold greater. Two cathepsin L activities identified in cercarial extracts by zymography co-migrated with activities in extracts of 3 h and 24 h schisotosomula and in extracts of adult worms. Since these enzymes have been implicated in haemoglob in digestion by adult worms, they may perform a similar function in schistosomula. Immunolocalization using scanning electron micrographs showed that cathepsin L and cathepsin B proteinases were present in the cercarial post-acetabular glands. In addition, cercarial serine proteinase activities considered to facilitate skin penetration efficiently cleaved the substrates Z-Gly-Pro-Arg-NHMec and Z-Gly-Pro-Lys-NHMec. Cercariae release most of this serine proteinase activity when induced to secrete the contents of their acetabular glands. In contrast, newly transformed 3 h and 24 h schistosomula did not express this activity.

Elevations of cathepsin B and cathepsin L activities in forelimb and hind limb muscles of genetically dystrophic mice

1986 ◽  
Vol 93 (3) ◽  
pp. 642-646 ◽  
Author(s):  
Keiji Komatsu ◽  
Kazutomo Tsukuda ◽  
Jun Hosoya ◽  
Susumu Satoh
Keyword(s):  
Cathepsin B ◽  
Hind Limb ◽  
Cathepsin L ◽  
Limb Muscles ◽  
Dystrophic Mice

scholarly journals Effects of microbial proteinase inhibitors on the degradation of endogenous and internalized proteins by rat yolk sacs

1981 ◽  
Vol 196 (1) ◽  
pp. 41-48 ◽  
Author(s):  
S E Knowles ◽  
F J Ballard ◽  
G Livesey ◽  
K E Williams
Keyword(s):  
Bovine Serum Albumin ◽  
Cathepsin B ◽  
Proteinase Inhibitors ◽  
Cathepsin L ◽  
Minor Role ◽  
Protein Breakdown ◽  
Inhibitory Effects ◽  
Endogenous Protein ◽  
A Minor

1. The effects of leupeptin and other microbial proteinase inhibitors were measured in rat yolk sacs on the uptake and degradation of formaldehyde-denatured 125I-labelled bovine serum albumin as well as on the degradation of 3H-labelled endogenous protein. 2. Leupeptin, at concentrations between 1 and 100 micrograms/ml, inhibits the degradation of added albumin without affecting pinocytic uptake. Accordingly large amounts of undegraded albumin accumulate within the tissue. 3. Removal of leupeptin produces a rapid recovery of the capacity to degrade albumin. 4. Endogenous protein degradation is rapidly inhibited by leupeptin, but to a far lesser extent than the breakdown of albumin. However, the inhibition is only slightly reversed on removal of leupeptin. 5. Degradation of both albumin and endogenous protein in intact yolk sacs is inhibited by the microbial proteinase inhibitors in the order: leupeptin greater than antipain greater than chymostatin; elastatinal, pepstatin and bestatin are ineffective. 6. Similar results are found when albumin is incubated in yolk-sac homogenates at pH 4 with the inhibitors. 7. The marked inhibitory effects of leupeptin, antipain and chymostatin suggest that cathepsin B and possibly cathepsin L participate in the degradation of 125I-labelled albumin in yolk sacs. By comparison, the smaller inhibitory effects of the proteinase inhibitors on endogenous protein breakdown imply a minor role of lysosomal cathepsins in this process.

scholarly journals Unique Subtype of Microglia in Degenerative Thalamus After Cortical Stroke

Stroke ◽  
2021 ◽  
Author(s):  
Zhijuan Cao ◽  
Sean S. Harvey ◽  
Terrance Chiang ◽  
Aulden G. Foltz ◽  
Alex G. Lee ◽  
...  
Keyword(s):  
Neurodegenerative Disease ◽  
Microglial Activation ◽  
Inflammatory Responses ◽  
Left Middle Cerebral Artery ◽  
Gene Expressions ◽  
Progressive Development ◽  
Permanent Occlusion ◽  
Cortical Stroke ◽  
Polymerase Chain ◽  
Neuronal Functions

Background and Purpose: Stroke disrupts neuronal functions in both local and remotely connected regions, leading to network-wide deficits that can hinder recovery. The thalamus is particularly affected, with progressive development of neurodegeneration accompanied by inflammatory responses. However, the complexity of the involved inflammatory responses is poorly understood. Herein we investigated the spatiotemporal changes in the secondary degenerative thalamus after cortical stroke, using targeted transcriptome approach in conjunction with histology and flow cytometry. Methods: Cortical ischemic stroke was generated by permanent occlusion of the left middle cerebral artery in male C57BL6J mice. Neurodegeneration, neuroinflammatory responses, and microglial activation were examined in naive and stroke mice at from poststroke days (PD) 1 to 84, in both ipsilesional somatosensory cortex and ipsilesional thalamus. NanoString neuropathology panel (780 genes) was used to examine transcriptome changes at PD7 and PD28. Fluorescence activated cell sorting was used to collect CD11c + microglia from ipsilesional thalamus, and gene expressions were validated by quantitative real-time polymerase chain reaction. Results: Neurodegeneration in the thalamus was detected at PD7 and progressively worsened by PD28. This was accompanied by rapid microglial activation detected as early as PD1, which preceded the neurodegenerative changes. Transcriptome analysis showed higher number of differentially expressed genes in ipsilesional thalamus at PD28. Notably, neuroinflammation was the top activated pathway, and microglia was the most enriched cell type. Itgax (CD11c) was the most significantly increased gene, and its expression was highly detected in microglia. Flow-sorted CD11c + microglia from degenerative thalamus indicated molecular signatures similar to neurodegenerative disease–associated microglia; these included downregulated Tmem119 and CX3CR1 and upregulated ApoE, Axl, LpL, CSF1, and Cst7. Conclusions: Our findings demonstrate the dynamic changes of microglia after stroke and highlight the importance of investigating stroke network-wide deficits. Importantly, we report the existence of a unique subtype of microglia (CD11c + ) with neurodegenerative disease–associated microglia features in the degenerative thalamus after stroke.

Cimaterol reduces cathepsin activities but has no anabolic effect in cultured myotubes

1990 ◽  
Vol 259 (6) ◽  
pp. E822-E827 ◽  
Author(s):  
D. M. Bechet ◽  
A. Listrat ◽  
C. Deval ◽  
M. Ferrara ◽  
J. F. Quirke
Keyword(s):  
Cathepsin B ◽  
Direct Action ◽  
Cathepsin L ◽  
Beta Agonist ◽  
Maximum Effect ◽  
Detectable Effect ◽  
Beta Agonists ◽  
Cathepsin H ◽  
Cultured Myotubes ◽  
Beta Adrenergic Agonist

The effect of the beta-adrenergic agonist cimaterol on bovine and chicken primary myotubes was assessed. Cimaterol at 10-100 nM concentrations reduced cathepsin B benzyloxy-carbonyl-Arg-Arg-4-methyl-7-coumarylamide hydrolyzing activity, as well as benzyloxycarbonyl-Phe-Arg-4-methyl-7-coumarylamide hydrolysis, which is a substrate for both cathepsin B and cathepsin L. Maximum effect was observed after 6-16 h treatment. Cathepsin H Arg-4-methyl-7-coumarylamide hydrolyzing activity was low and not significantly affected by cimaterol treatment. Despite decreasing cathepsin activities, cimaterol also increased proteolysis rates but induced no detectable effect on protein synthesis rates. These observations suggest that beta-agonists, as a result of a direct action on muscle, can decrease cathepsin activities but that beta-agonist-induced muscle hypertrophy may not be due to a direct effect on muscle cells.

Purification and properties of different isoforms of bovine cathepsin B

1990 ◽  
Vol 68 (4) ◽  
pp. 822-826 ◽  
Author(s):  
Christiane Deval ◽  
Daniel Bechet ◽  
Alain Obled ◽  
Marc Ferrara
Keyword(s):  
Cathepsin B ◽  
Cathepsin L ◽  
Gel Filtration ◽  
Specific Inhibitor ◽  
Bovine Liver ◽  
Relative Mass ◽  
Low Concentrations ◽  
Purification And Properties ◽  
Different Populations ◽  
Rapid Purification

A rapid purification procedure is described for cathepsin B from bovine liver. After preparation of crude lysosomal extracts, the method only involves DEAE Zeta-Prep-Disk chromatography, gel filtration, and fast protein liquid chromatography on Mono-S column. Two active peaks (P1 and P2) of cathepsin B were distinguished. Both presented uncleaved (relative mass (Mr) 30 000) and cleaved (Mr 25 000 + Mr 5000) chains, but different isoforms as revealed by isoelectrofocusing. These two different populations of cathepsin B isoforms nevertheless exhibited similar enzymatic properties. Km and kcat were 114 μM and 52 s−1, and 125 μM and 75 s−1, for hydrolysis of Z-Arg-Arg-NMec by P1 and P2, respectively. Both were rapidly inhibited by low concentrations of E-64 or leupeptin, but were unaffected by cathepsin-L-specific inhibitor Z-Phe-Phe-CHN2.Key words: protein/enzyme purification, cathepsin B, isoforms, lysosomes.

scholarly journals The identification of active forms of cysteine proteinases in Kirsten-virus-transformed mouse fibroblasts by use of a specific radiolabelled inhibitor

1989 ◽  
Vol 257 (1) ◽  
pp. 125-129 ◽  
Author(s):  
R W Mason ◽  
D Wilcox ◽  
P Wikstrom ◽  
E N Shaw
Keyword(s):  
Cathepsin B ◽  
Cathepsin L ◽  
Active Form ◽  
Culture Conditions ◽  
Secreted Protein ◽  
Cysteine Proteinases ◽  
Tumour Invasion ◽  
Specific Antibodies ◽  
Mouse Fibroblasts

The major active forms of cathepsins B and L were identified in Kirsten-virus-transformed mouse fibroblasts by the use of a specific radiolabelled inhibitor, benzyloxycarbonyl-Tyr(-125I)-Ala-CHN2. No other proteins were labelled, demonstrating the specificity of this inhibitor for cysteine proteinases. Cathepsins B and L were distinguished by the use of specific antibodies. One active form of cathepsin B, Mr 33,000-35,000, and two active forms of cathepsin L, Mr 30,000 and 23,000, were identified. The intracellular precursors of these proteins had higher Mr values of 39,000 and 36,000 for cathepsins B and L respectively, as shown by pulse-chase experiments with [35S]methionine-labelled proteins. These did not react with the inhibitor under our culture conditions. The precursor of cathepsin L was secreted whereas the precursor of cathepsin B was not, demonstrating that secretions of the two enzymes are regulated differently. In contrast with results found previously for the purified protein [Mason, Gal & Gottesman (1987) Biochem. J. 248, 449-454], the secreted precursor form of cathepsin L did not react with the inhibitor either, indicating that it is not active and therefore, as such, cannot be directly involved in tumour invasion. The secreted protein did react with the inhibitor when incubated at pH 3.0, showing that the protein can be activated, although this did not occur under our culture conditions.

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